Interface Engineering of "Clickable" Organic Electrochemical Transistors toward Biosensing Devices.

"Clickable" organic electrochemical transistors (OECTs) allow the reliable and straightforward functionalization of electronic devices through the well-known click chemistry toolbox. In this work, we study various aspects of the click chemistry-based interface engineering of "clickable" OECTs. First, different channel architectures are investigated, showing that PEDOT-N3 films can properly work as a channel of the transistors. Furthermore, the Cu(I)-catalyzed click reaction of ethynyl-ferrocene is studied under different reaction conditions, endowing the spatial control of the functionalization. The strain-promoted and catalyst-free cycloaddition of a dibenzocyclooctyne-derivatized poly-l-lysine (PLL-DBCO) is also performed on the OECTs and validated by a fiber optic (FO)-SPR setup. The further immobilization of an azido-modified HD22 aptamer yields OECT-based biosensors that are employed for the recognition of thrombin. Finally, their performance is evaluated against previously reported architectures, showing higher density of the immobilized HD22 aptamer, and originating similar KD values and higher maximum signal change upon analyte recognition.

Correction to "'Clickable' Organic Electrochemical Transistors".

[This corrects the article DOI: 10.1021/jacsau.2c00515.].

"Clickable" Organic Electrochemical Transistors.

Interfacing the surface of an organic semiconductor with biological elements is a central quest when it comes to the development of efficient organic bioelectronic devices. Here, we present the first example of "clickable" organic electrochemical transistors (OECTs). The synthesis and characterization of an azide-derivatized EDOT monomer (azidomethyl-EDOT, EDOT-N3) are reported, as well as its deposition on Au-interdigitated electrodes through electropolymerization to yield PEDOT-N3-OECTs. The electropolymerization protocol allows for a straightforward and reliable tuning of the characteristics of the OECTs, yielding transistors with lower threshold voltages than PEDOT-based state-of-the-art devices and maximum transconductance voltage values close to 0 V, a key feature for the development of efficient organic bioelectronic devices. Subsequently, the azide moieties are employed to click alkyne-bearing molecules such as redox probes and biorecognition elements. The clicking of an alkyne-modified PEG4-biotin allows for the use of the avidin-biotin interactions to efficiently generate bioconstructs with proteins and enzymes. In addition, a dibenzocyclooctyne-modified thrombin-specific HD22 aptamer is clicked on the PEDOT-N3-OECTs, showing the application of the devices toward the development of organic transistors-based biosensors. Finally, the clicked OECTs preserve their electronic features after the different clicking procedures, demonstrating the stability and robustness of the fabricated transistors.

Broadly Applicable Synthesis of Arylated Dithieno[3,2-b:2',3'-d]pyrroles as Building Blocks for Organic Electronic Materials.

A novel and versatile method for the N-arylation of dithieno[3,2-b:2',3'-d]pyrrole (DTP) is presented. By Pd- or Cu-catalyzed coupling a variety of arenes and acenes were directly attached at the DTP-nitrogen yielding a variety of functionalized DTPs. Investigations on optical and redox properties led to valuable structure-property relationships, which were corroborated by quantum chemical calculations. Further functionalization and elongation of the conjugation of an acceptor-substituted DTP was elaborated to result in complex cruciform-type donor-acceptor oligomers, which were investigated and implemented in single material organic solar cells.

Design and Synthesis of Fsp(3)-Rich, Bis-Spirocyclic-Based Compound Libraries for Biological Screening.

The exploration of innovative chemical space is a critical step in the early phases of drug discovery. Bis-spirocyclic frameworks occur in natural products and other biologically relevant metabolites and show attractive features, such as molecular compactness, structural complexity, and three-dimensional character. A concise approach to the synthesis of bis-spirocyclic-based compound libraries starting from readily available commercial reagents and robust chemical transformations has been developed. A number of novel bis-spirocyclic scaffold examples, as implemented in the European Lead Factory project, is presented.

Design and synthesis of 1,1-disubstituted-1-silacycloalkane-based compound libraries.

The introduction of silicon in biologically-relevant molecules represents an interesting medicinal chemistry tactic. Its use is mainly confined to the fine-tuning of specific molecular properties and organosilicon compounds are underrepresented in typical screening libraries. As part of the European Lead Factory efforts to generate novel, drug discovery-relevant chemical matter, the design and synthesis of 1,1-disubstituted-1-silacycloalkane-based compound libraries is described.

Growth of PtRu clusters on Ru(0001)-supported monolayer graphene films.

We report on results of a detailed scanning tunnelling microscopy study on the formation, size and size distribution, and internal structure of small bimetallic PtRu clusters on a graphene monolayer film supported on a Ru(0001) substrate. These clusters, with sizes around ∼15 (Ru) or ∼40 (Pt) atoms per cluster at the lowest coverage, are interesting model systems for the catalytic behaviour of small metal PtRu particles, for example for application in electrocatalytic oxidation reactions. The clusters were generated by sequential deposition of the two metals at room temperature. The data reveal a distinct influence of the deposition sequence on the cluster formation process, with Ru pre-deposition followed by Pt deposition leading to predominantly bimetallic clusters, possibly with a core-shell-type structure, while the reverse sequence results in co-existent mono- and bimetallic clusters, where the latter are likely to intermix at the interface. The observations are related to the nucleation process of the respective metals on the templated surface, and the 2D growth behaviour of the two metals.

A comparison of conventional and retrospective measures of change in symptoms after elective surgery.

BACKGROUND: Measuring change is fundamental to evaluations, health services research and quality management. To date, the Gold-Standard is the prospective assessment of pre- to postoperative change. However, this is not always possible (e.g. in emergencies). Instead a retrospective approach to the measurement of change is one alternative of potential validity. In this study, the Gold-Standard 'conventional' method was compared with two variations of the retrospective approach: a perceived-change design (model A) and a design that featured observed follow-up minus baseline recall (model B). METHODS: In a prospective longitudinal observational study of 185 hernia patients and 130 laparoscopic cholecystectomy patients (T0: 7-8 days pre-operative; T1: 14 days post-operative and T2: 6 months post-operative) changes in symptoms (Hernia: 9 Items, Cholecystectomy: 8 Items) were assessed at the three time points by patients and the conventional method was compared to the two alternatives. Comparisons were made regarding the percentage of missing values per questionnaire item, correlation between conventional and retrospective measurements, and the degree to which retrospective measures either over- or underestimated changes and time-dependent effects. RESULTS: Single item missing values in model A were more frequent than in model B (e.g. Hernia repair at T1: model A: 23.5%, model B: 7.9%. In all items and at both postoperative points of measurement, correlation of change between the conventional method and model B was higher than between the conventional method and model A. For both models A and B, correlation with the change calculated with the conventional method was higher at T1 than at T2. Compared to the conventional model both models A and B also overestimated symptom-change (i.e. improvement) with similar frequency, but the overestimation was higher in model A than in model B. In both models, overestimation was lower at T1 than at T2 and lower after hernia repair than after cholecystectomy. CONCLUSIONS: The retrospective method of measuring change was associated with a larger improvement in symptoms than was the conventional method. Retrospective assessment of change results in a more optimistic evaluation of improvement by patients than does the conventional method (at least for hernia repair and laparoscopic cholecystectomy).

Assessing patient-reported outcomes of cholecystectomy in short-stay surgery.

BACKGROUND: The project aimed at testing the feasibility of a quality improvement system based on patient-reported outcomes in short-stay surgery for cholecystectomy. METHODS: In two centers for short-stay surgery, patients referred for laparoscopic cholecystectomy were surveyed between Aug 1999 and Jan 2002. Patients reported on health-related quality of life (SF-36), symptoms (gallstone symptom checklist, GSCL) and other indicators preoperatively (T0), 14 days (T1) and 6 months postoperatively (T2). The SF-36 subscales physical functioning, bodily pain, and role physical as well as the GSCL and treatment satisfaction at T2 were considered as main outcomes. The main outcomes were analyzed by generalized linear models with regard to predictors. RESULTS: At T0 a total of 205 patients were included. The response rate at T2 was 63.4% (74.6% females, 53.6 years of age). The GSCL score at T0 (29.4% preoperatively) fell slightly to 27.9% at T1 and decreased to 14.8% at T2 (T0-T2: p < 0.001). The SF-36 subscales showed a different course over time (decrease of health-related quality of life at T1 and large increase at T2). The level of satisfaction with the outcome of cholecystectomy was 82.3%. The patient-reported outcomes were mainly influenced by the preoperative level, age and self-reported postoperative complaints. CONCLUSION: The low response rate was mainly due to nondelivery of questionnaires at T1 during the regular postoperative visit by the operating physician. Though nonresponse occurs under conditions of routine care, meaningful information was gained, which should be used for quality improvement activities. Because the preoperative level is a major determinant of the postoperative health outcomes, the prospective pre-post measurement should be preferred if institutional comparisons are intended.

[Patient reported process and outcome indicators for clinical audit in short-stay surgery]. / Prozess- und ergebnis-orientiertes Qualitäts-management in der Kurzzeitchirurgie mit Patientenbefragungen.

BACKGROUND: Based on patient-reported process and outcome indicators of care, a system for quality improvement in short-stay surgery was developed for hernia repair and cholecystectomy. The study aimed to test the feasibility and validity of the system. METHODS: In two centres for short-stay surgery all patients referred for hernia repair or cholecystectomy were surveyed between August 1999 and January 2002 (T0: preoperative, T1: 14 days post-OP, T2: 6 months post-OP). At T0 and T1 survey instruments were given to patients in the participating centres, at T2 the survey instruments were mailed. Of 342 hernia patients and 250 cholecystolithiasis patients at T0, responses from only 54.1% (hernia) and 63.4% (cholecystolithiasis) were available at T2. Non-response predominantly occurred between T0 and T1. Patients reported on satisfaction with care (FKKP), health-related quality of life (HRQL; SF-36), disease-specific symptoms (symptom checklists), treatment satisfaction and other indicators. RESULTS: Satisfaction with care was quite high. The process indicator of the lowest satisfaction was the provision of competencies to deal with problems at home after discharge at home. At T2 21.1% (hernia) and 66.2% (cholecystolithiasis) reported no complications. Both symptom checklists reflect the positive postoperative course (effect size T0-T2: 1.16 and 0.75). From a T0 level lower than the German reference population (six of the eight SF-36 subscales) HRQL reaches or exceeds the population norms at T2. CONCLUSION: In general, both the proposed proceedings and the instrument were applicable and feasible. Patient-oriented quality indicators contain additional information on processes and outcomes of care. However, the participating centres were not fully prepared to spend the extra effort necessary to organise such a longitudinal survey. To decrease non-response between T0 and T1, survey instruments should be mailed at T1 (instead of handing them over to patients during their postoperative visit).